ABBV-383 for Multiple Myeloma

Recruiting at 60 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: Proteasome inhibitors, IMiDs, Anti-CD38

Must not be taking: BCMA-targeted therapy

Disqualifiers: Rapidly progressing disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ABBV-383, for individuals with multiple myeloma, a type of blood cancer, to determine its effectiveness when other treatments have failed or the cancer has returned. The study consists of three parts to evaluate different methods of administering the drug. Participants will receive the drug through an IV (a tube in the vein) every 28 days for about three years. It targets those who have previously undergone several treatments, including specific types like a proteasome inhibitor and an immunomodulatory drug. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ABBV-383, a new drug being tested for relapsed or refractory multiple myeloma, appears promising in early studies. ABBV-383 is a treatment that helps the immune system attack cancer cells.

Early results suggest that ABBV-383 is generally safe for patients. Some studies found that patients experienced mild to moderate side effects, which were manageable. Since this trial is in its early stages, the main goal is to assess the safety of ABBV-383. Its progression in clinical trials suggests that serious side effects are probably uncommon. However, ongoing trials remain crucial to ensure its safety and effectiveness before widespread use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ABBV-383 for multiple myeloma because it introduces a new approach targeting the B-cell maturation antigen (BCMA). Unlike traditional treatments, which often involve chemotherapy or proteasome inhibitors, ABBV-383 aims directly at BCMA, a protein commonly found on the surface of myeloma cells. This BCMA-targeting mechanism allows it to directly attack the cancer cells more precisely. Additionally, ABBV-383 can be used in patients previously exposed to BCMA-targeted therapies and in BCMA-naïve patients, offering a tailored approach that could potentially enhance its effectiveness across different patient groups.

What evidence suggests that this trial's treatments could be effective for relapsed/refractory multiple myeloma?

Research has shown that ABBV-383 may help treat relapsed or refractory multiple myeloma. This drug targets a protein called BCMA on cancerous plasma cells, prompting the immune system to attack these cells. Early results suggest that ABBV-383 connects with both cancer and immune cells, aiding the immune system in destroying the cancer. Although still in early testing, this method has shown promise in reducing tumor size. Participants in this trial will receive ABBV-383 in different treatment arms, including those previously exposed to BCMA-targeted agents and those who are BCMA naïve, to evaluate its effectiveness across various patient groups. It is designed to work even when other treatments have not. ^{1 2 3 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with Multiple Myeloma that has returned or hasn't improved after treatment can join. They must have had at least 2-3 prior treatments, including specific drugs like proteasome inhibitors and anti-CD38 antibodies. For one part of the study, they shouldn't have had BCMA-targeted therapy before.

Inclusion Criteria

You must have a disease that can be measured according to the study guidelines.

I have never been treated with ABBV-383.

I've had 3+ treatments including PI, IMiD, and anti-CD38 for my condition.

Exclusion Criteria

I have received therapy targeting BCMA.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-383 as an infusion into the vein in 28 day cycles for approximately 3 years

3 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-383

Trial Overview

The trial is testing ABBV-383, a new drug for relapsed/refractory Multiple Myeloma. It's given by IV in two parts: first finding the right starting dose then expanding to more patients; another group gets a fixed dose. The study lasts about 3 years with regular hospital visits.

How Is the Trial Designed?

Group I: Arm C: ABBV-383 Step Up Experimental Treatment 1 Intervention

Participants will receive step up dose and full target dose of ABBV-383 in 28 day cycles.

Group II: Arm B: ABBV-383 BCMA Exposed Experimental Treatment 1 Intervention

Participants previously exposed to BCMA-targeted agents will receive ABBV-383 Dose A in 28 day cycles.

Group III: Arm A (Part 2): ABBV-383 Dose Expansion Experimental Treatment 1 Intervention

BCMA naïve participants will receive the dose of ABBV-383 dose A in 28 day cycles.

Group IV: Arm A (Part 1): ABBV-383 Dose Escalation Experimental Treatment 1 Intervention

B-cell maturation antigen (BCMA) naïve participants will receive different doses of ABBV-383 in 28 day cycles.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

TeneoOne Inc.

Lead Sponsor

Trials

5

Recruited

860+

Published Research Related to This Trial

ABBV-383, a bispecific antibody targeting B-cell maturation antigen and CD3, showed a promising overall response rate (ORR) of 68% in patients with relapsed/refractory multiple myeloma (RRMM) at doses of 40 mg or higher, indicating its potential efficacy as a treatment option.

The treatment was generally well tolerated, with common side effects including neutropenia (37%) and cytokine release syndrome (57%), and no deaths were deemed related to the study drug, suggesting a favorable safety profile for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. D'Souza, A., Shah, N., Rodriguez, C., et al.[2023]

The study developed several bispecific BCMA-CD3 antibodies that effectively target and kill multiple myeloma cells, demonstrating specific binding and cytotoxic activity in vitro with a strong affinity in the nanomolar range.

In vivo testing in a mouse model showed that these BCMA bispecific antibodies had high efficacy against multiple myeloma, supporting their potential for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Wu, L., Huang, Y., Sienkiewicz, J., et al.[2022]

The fully human bispecific antibody REGN5458, which targets B-cell maturation antigen (BCMA) and CD3, effectively induces T-cell killing of multiple myeloma cells and shows strong antitumor activity in mouse models, demonstrating its potential as a rapid therapeutic option.

In head-to-head comparisons, REGN5458 cleared tumors more quickly than anti-BCMA CAR T cells, suggesting that bispecific antibodies can engage existing T cells at the tumor site for immediate action, while CAR T cells require time to activate and expand before they can attack the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. DiLillo, DJ., Olson, K., Mohrs, K., et al.[2021]

Bispecific antibodies (BsAbs) and dual-targeted CAR T cells have shown promising results in treating relapsed/refractory multiple myeloma (RRMM) patients, particularly those who have not responded to at least three prior therapies.

Recent data from the 2023 ASCO annual meeting highlight that combinations targeting BCMA/CD3 and GPRC5D/CD3 lead to stronger and more durable responses in patients, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. Hou, J., Li, Y., Lin, Q.[2023]

The bispecific antibody BiFab-BCMA effectively redirects T cells to attack multiple myeloma cells, showing up to 20 times greater potency than a similar antibody targeting CS1.

BiFab-BCMA not only activates T cells in laboratory settings but also leads to rapid tumor regression in animal models, suggesting it could be a promising alternative to existing CAR-T therapies for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. Ramadoss, NS., Schulman, AD., Choi, SH., et al.[2015]

TNB-383B effectively induces the killing of plasma cells in bone marrow from patients with relapsed multiple myeloma, showing dose-dependent lysis starting at very low doses (0.001 μg).

The treatment leads to significant degranulation of cytotoxic T lymphocytes (CTLs) and modulates cytokine responses, with notable increases in IL-2/TNFα and IP10, indicating a robust immune response without significant T cell expansion or severe cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. Foureau, DM., Bhutani, M., Robinson, M., et al.[2023]

Citations

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news.abbvie.com

news.abbvie.com/2024-06-05-AbbVie-Advances-Oncology-Pipeline-With-Start-of-Multiple-Myeloma-Phase-3-Clinical-Trial-for-Investigational-Asset-ABBV-383

AbbVie Advances Oncology Pipeline With Start of Multiple ...

ABBV-383 is a distinctive B-cell maturation antigen (BCMA) and CD3 bispecific antibody T-cell engager composed of bivalent BCMA-binding domains ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.22.01504

A Phase I First-in-Human Study of ABBV-383, a B-Cell ...

ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study.

3.

cancer.gov

cancer.gov/publications/dictionaries/cancer-drug/def/etentamig

Definition of anti-BCMA/anti-CD3 T-cell engaging bispecific ...

Upon administration, anti-BCMA/anti-CD3 T-cell engaging bispecific antibody ABBV-383 binds to both CD3 on cytotoxic T lymphocytes (CTLs) and BCMA found on BCMA- ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03933735

NCT03933735 | A Study of TNB-383B in Participants With ...

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9175895/

Ex vivo efficacy of BCMA‐bispecific antibody TNB‐383B in ...

TNB‐383B is a fully human BCMA‐targeting T‐cell engaging bispecific monoclonal antibody (T‐BsAb). We assessed ex vivo efficacy of this drug to mediate killing ...

6.

multiplemyelomahub.com

multiplemyelomahub.com/medical-information/abbv-383-a-novel-bcmacd3-bispecific-antibody-for-the-treatment-of-rrmm

ABBV-383, a novel BCMA/CD3 bispecific antibody for the ...

ABBV-383 will provide high efficacy for the treatment of relapsed/refractory multiple myeloma (RRMM), and be well tolerated, especially through the mitigation ...

7.

abbvieclinicaltrials.com

abbvieclinicaltrials.com/study/?id=TNB383B.0001

A Study of TNB-383B in Participants With Relapsed or ...

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific ...